Is physical activity a cause of longevity? It is not as straightforward as some would believe. A critical analysis

Kujala, Urho M.

doi:10.1136/bjsports-2017-098639

Cited by 62 publications

(64 citation statements)

References 69 publications

(36 reference statements)

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“…9b). It should be noted that, in both humans and mice, endurance exercise training improves healthspan but is not effective for extending maximal lifespan 57,58 . Also in flies, exercise training improved running capacity and flight performance 27 , but did not increase longevity 59 .…”

Section: Discussionmentioning

confidence: 99%

Sestrins are evolutionarily conserved mediators of exercise benefits

et al. 2020

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Exercise is among the most effective interventions for age-associated mobility decline and metabolic dysregulation. Although long-term endurance exercise promotes insulin sensitivity and expands respiratory capacity, genetic components and pathways mediating the metabolic benefits of exercise have remained elusive. Here, we show that Sestrins, a family of evolutionarily conserved exercise-inducible proteins, are critical mediators of exercise benefits. In both fly and mouse models, genetic ablation of Sestrins prevents organisms from acquiring metabolic benefits of exercise and improving their endurance through training. Conversely, Sestrin upregulation mimics both molecular and physiological effects of exercise, suggesting that it could be a major effector of exercise metabolism. Among the various targets modulated by Sestrin in response to exercise, AKT and PGC1α are critical for the Sestrin effects in extending endurance. These results indicate that Sestrin is a key integrating factor that drives the benefits of chronic exercise to metabolism and physical endurance.

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Section: Discussionmentioning

confidence: 99%

Sestrins are evolutionarily conserved mediators of exercise benefits

et al. 2020

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“…10 26-28 It is well established that PA improves fitness and physical function. 29 Original article Table 3 Association between leisure time physical activity level and the risk of all-cause and cause-specific mortality by intensity of activity performance and cardiac function, and were beneficial for weight loss, 30 which may help explain why PA decreased the risk of CVD mortality. The protective effects of PA on cancer mortality have also been widely established in previous studies.…”

Section: Discussionmentioning

confidence: 99%

Beneficial associations of low and large doses of leisure time physical activity with all-cause, cardiovascular disease and cancer mortality: a national cohort study of 88,140 US adults

Zhao

Veeranki

Li³

et al. 2019

Br J Sports Med

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BackgroundEvidence on the role of very low or very high volumes of leisure time physical activity (PA) on the risk of all-cause and cause-specific mortality is limited. We aimed to examine the associations of different levels of leisure time PA with the risk of all-cause, cardiovascular disease (CVD) and cancer-specific mortality.MethodsData were from 12 waves of the National Health Interview Surveys (1997–2008) linked to the National Death Index records through 31 December 2011. A total of 88 140 eligible participants aged 40–85 years were included.ResultsCompared with inactive individuals, those performing 10–59 min/week of PA had 18% lower risk of all-cause mortality (hazard ratio (HR): 0.82, 95% confidence interval (CI): 0.72–0.95). Those who reported 1–2 times (150–299 min/week) the recommended level of leisure time PA had 31% (HR: 0.69, 95%CI: 0.63–0.75) reduced risk of all-cause mortality. Importantly, the continued benefits were observed among those performing leisure time PA 10 or more times (≥1500 min/week) the recommended minimum level (HR: 0.54, 95% CI: 0.45–0.64). For 10–59, 150–299 and ≥1500 min/week of PA, the corresponding HRs (95% CIs) for CVD-specific mortality were 0.88 (0.67–1.17), 0.63 (0.52–0.78) and 0.67 (0.45–0.99), respectively: for cancer-specific mortality were 0.86 (0.66–1.11), 0.76 (0.64–0.89) and 0.53 (0.39–0.73), respectively. In addition, there was a larger reduction in all-cause and cause-specific mortality for vigorous vs. moderate intensity PA.ConclusionsWe found that beneficial association between leisure time PA and mortality starts from a low dose. Doing more vigorous exercise could lead to additional health benefits.

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“…[1][2][3][4] It remains difficult, however, to firmly establish the causal nature of these associations since reverse causation, residual confounding, and selection biases are inherent limitations of observational data. 5,6 Randomised controlled exercise trials are a better test of causation, but these studies cannot realistically follow initially healthy participants for long periods of time in order to track incident disease risk. Trials also tend to be highly structured and thus unreflective of usual physical activity patterns.…”

Section: Introductionmentioning

confidence: 99%

Examining associations between physical activity and cardiovascular mortality using negative control outcomes

Hamer

Bauman

Bell

et al. 2018

International Journal of Epidemiology

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Background The purpose of a negative control is to reproduce a condition that cannot involve the hypothesized causal mechanism, but does involve the same sources of bias and confounding that may distort the primary association of interest. Observational studies suggest physical inactivity is a major risk factor for cardiovascular disease (CVD), although potential sources of bias, including reverse causation and residual confounding, make it difficult to infer causality. The aim was to employ a negative control outcome to explore the extent to which the association between physical activity and CVD mortality is explained by confounding. Methods The sample comprised 104 851 participants (aged 47 ± 17 years; 45.4% male) followed up over mean (SD) 9.4 ± 4.5 years, recruited from the Health Survey for England and the Scottish Health Survey. Results There were 10 309 deaths, of which 3109 were attributed to CVD and 157 to accidents (negative control outcome). Accidental death was related to age, male sex, smoking, longstanding illness and psychological distress, with some evidence of social patterning. This confounding structure was similar to that seen with CVD mortality, suggesting that our negative control outcome was appropriate. Physical activity (per SD unit increase in MET-hr-wk) was inversely associated with CVD [hazard ratio (HR) = 0.75; 95% confidence interval (CI), 0.70, 0.80]; the point estimate between physical activity and accidental death was in the same direction but of lesser magnitude (HR = 0.86; 95% CI: 0.69, 1.07). A linear dose–response pattern was observed for physical activity and CVD but not with the negative control. Conclusions Inverse associations between physical activity and risk of CVD mortality are likely causal but of a smaller magnitude than commonly observed. Negative control studies have the potential to improve causal inference within the physical activity field.

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Is physical activity a cause of longevity? It is not as straightforward as some would believe. A critical analysis

Cited by 62 publications

References 69 publications

Sestrins are evolutionarily conserved mediators of exercise benefits

Sestrins are evolutionarily conserved mediators of exercise benefits

Beneficial associations of low and large doses of leisure time physical activity with all-cause, cardiovascular disease and cancer mortality: a national cohort study of 88,140 US adults

Examining associations between physical activity and cardiovascular mortality using negative control outcomes

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